Study of Olaparib/Trabectedin vs. Doctor's Choice in Solid Tumors

NCT03127215 | Completed Phase 2 DMC

• 1 other identifier: NCT-2017-0417
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 9

Brief Summary

Evaluation of the efficacy of the combination of olaparib and trabectedin in adult patients with locally advanced/metastatic solid tumors that failed standard treatment and whose molecular sequencing tumor profiles show homologous recombination repair (HRR) defects. The primary objective is to show superior disease control rate in patients with HRR-deficient tumors treated with olaparib and trabectedin compared to treatment according to current guidelines (physician's choice). This trial aims to establish whether the PARP-dependency of HRR-deficient tumors across entities can be exploited for therapeutic benefit.

Conditions

Cancers With DNA Repair-Deficiency

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate

  Randomized, open-label, multicenter phase-II study comparing olaparib in combination with trabectedin versus physician's choice. Primary efficacy endpoint is the disease control rate after 5 cycles.

  At week 16 (after 5 cycles of study medication)

Secondary Outcomes (4)

• Overall survival

  Time from first administration of the IMP to time death from any cause until end of study (2.5 years)

• Incidence of Treatment-Emergent Adverse Events

  Time from first administration of the IMP to subjects end of trial (approximately month 6)

• Patient reported outcomes

  Before the first (week 0), at the third (week 8), and after the fifth treatment cycle (week 16)

• Tumor response rate

  At week 16 (after 5 cycles of study medication)

Study Arms (2)

Arm E: Olaparib / Trabectedin

EXPERIMENTAL

Olaparib / Trabectedin

Drug: Olaparib; Drug: Trabectedin

Arm C: Physician's choice

OTHER

Physician's choice

Drug: Physician's choice

Interventions

Olaparib DRUG

Olaparib 150 mg tablet

Arm E: Olaparib / Trabectedin

Physician's choice DRUG

treatment according to current guidelines

Arm C: Physician's choice

Trabectedin DRUG

Trabectedin 1.1mg/m² infusional solution

Arm E: Olaparib / Trabectedin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Progressive locally advanced or metastatic malignancy
• Prior administration of standard treatment for primary and relapsed malignancy
• Eastern Cooperative Oncology Group Performance Status ≤1
• Patients with central venous access device in place (central venous catheter or porta-cath)
• Age ≥18 and ≤70 years
• Identification of defective DNA repair via HR
• Adequate bone marrow, renal, and hepatic function
• Hemoglobin ≥10 g/dl
• Neutrophil count ≥1,500/mm3
• Platelet count ≥100,000/µl
• Bilirubin ≤1.5 x upper limit of normal (ULN)
• ALT and AST ≤2.5 x ULN (≤5 x ULN in patients with hepatic tumor involvement)
• Alkaline phosphatase ≤2.5 x ULN
• PT-INR/PTT ≤1.5 x ULN

You may not qualify if:

• Hematological malignancies and primary brain tumors.
• Concurrent treatment in another interventional clinical trial
• Prior treatment with PARP Inhibitors
• Patients with platinum-refractory disease, defined as progressive disease during or immediately after treatment with platinum based chemotherapy
• Persistent toxicity (\> Grade 2 according to CTCAE 5.0)
• Dementia or significant impairment of cognitive state
• History of HIV infection
• Clinical signs of active infection (\>Grade 2 according to CTCAE 4.03)
• History of viral hepatitis (HBV or HCV)
• Epilepsy requiring pharmacologic treatment
• Pregnancy
• Known hypersensitivity to any of the study drugs
• Hematologic malignancy
• QTc time prolongation \>500 ms or history of familial long-QT-syndrome
• Heart failure NYHA III/IV

Sponsors & Collaborators

• National Center for Tumor Diseases, Heidelberg: lead
• AstraZeneca: collaborator
• PharmaMar: collaborator
• German Cancer Research Center: collaborator

Study Sites (9)

Medizinische Fakultät der TU Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

National Center for Tumordiseases (NCT)

Heidelberg, 69120, Germany

Location

Universitätsmedizin der Johannes-Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Klinikum der Universität München-Großhadern

München, 81377, Germany

Location

Klinik Schillerhöhe

Stuttgart, 70376, Germany

Location

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

Location

MeSH Terms

Interventions

olaparib; Trabectedin

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Stefan Froehling, MD

  NCT / DKFZ Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: open label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized

Study Record Dates

• First Submitted: March 31, 2017
• First Posted: April 25, 2017
• Study Start: October 25, 2018
• Primary Completion: December 19, 2023
• Study Completion: December 19, 2023
• Last Updated: May 8, 2024

Record last verified: 2023-08

Locations

DE (9)